Tuesday, April 8, 2008

Reshaping DNA could reshape your life

According to recent findings at the University of Illinois, Chicago, reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in the alcohol withdrawal symptoms, particularly anxiety, that make it so difficult for alcoholics to stop using alcohol.

"This is the first time anyone has looked for epigenetic changes related to chromatin remodelling in the brain during alcohol addiction," said Dr. Subhash C. Pandey, professor and director of neuroscience alcoholism research at the UIC College of Medicine and the Jesse Brown VA Medical Centre in Chicago, the lead author of the study.

These ‘epigenetic’ changes are minor chemical modifications of chromatin and have been previously found to alter anxiety and alcohol-drinking behaviour in animal models. Chemical modification of histones, which are proteins contained in the chromatin, can change the way DNA and histones are wound up together. Histone acetyltransferases (HATs) are enzymes that add acetyl groups to histones and loosen the packing, promoting gene expression. On the other hand, histone deacetylases (HDACs) remove acetyl groups from histones, causing them to wrap with DNA more tightly, decreasing gene expression.

In this new study, the conductors looked at the HDAC activity, acetylation of histones, and expression of the genes for NPY in the amygdala and the anxiety-like behaviours associated with withdrawal from chronic alcohol use. They found that acute exposure to alcohol decreases HDAC activity; increases the acetylation histones; increases levels of NPY – and subsequently reduced anxiety in the animals. On the other hand, anxiety-like behaviours during withdrawal in animals with chronic alcohol exposure were associated with an increase in HDAC activity and decrease in histones acetylation and NPY levels. Most importantly, it was found that the development of anxiety-like behaviours during alcohol withdrawal could be prevented by blocking the observed increase in HDAC activity using an HDAC inhibitor and causing histone acetylation and NPY expression levels in the amygdala to increase also.

"Our findings suggest that HDAC inhibitors may have potential as therapeutic agents in treating alcoholism," Pandey said. "We need new strategies to treat alcoholism that are directed toward the prevention of withdrawal symptoms. Anxiety associated with withdrawal from alcohol abuse is a key factor in the maintenance of alcohol addiction."